Theranostics Revolutionizes Neuroendocrine Neoplasm Management via Peptide Receptor Radionuclide Therapy

Managing Neuroendocrine neoplasms (NENs) presents significant challenges due to their heterogeneous nature and often advanced stage at diagnosis. Traditional treatments, while effective for some, frequently encounter limitations in specificity and systemic toxicity, leaving a critical gap for targeted, personalized approaches. Peptide receptor radionuclide therapy (PRRT), a form of theranostics, leverages the overexpression of somatostatin receptors (SSTRs) on NEN cells, offering a highly specific strategy to both image and treat these complex cancers, thereby addressing the need for improved precision oncology.

This comprehensive review systematically examined the current landscape of theranostics in Neuroendocrine neoplasms (NENs), integrating molecular functional imaging with targeted radionuclide therapy. The authors detailed the molecular basis of somatostatin receptor (SSTR) targeting, covering both diagnostic imaging modalities and therapeutic radiopharmaceuticals. The review meticulously analyzed various dosimetry methodologies, patient selection criteria, and reported treatment outcomes. Furthermore, it scrutinized toxicity profiles associated with current theranostic approaches and explored emerging innovations, including the use of α-emitting radionuclides and novel SSTR antagonists to enhance therapeutic efficacy.

The review highlights that theranostics, particularly peptide receptor radionuclide therapy (PRRT), has profoundly transformed NEN management by integrating precise imaging with targeted therapy. It underscores the critical role of somatostatin receptor (SSTR) expression, especially SSTR2, as a foundational biomarker for patient selection and therapeutic guidance. The synthesis of evidence demonstrates that PRRT with β-emitting radionuclides like 177Lu-DOTATATE achieves significant tumor responses and improved progression-free survival in patients with advanced NENs, often with manageable toxicity profiles. Emerging data on α-emitting radionuclides (e.g., 225Ac-DOTATATE) suggests enhanced cytotoxic potential due to their high linear energy transfer, offering promise for patients with extensive disease or resistance to β-emitters. The review also emphasizes the evolving importance of personalized dosimetry to optimize therapeutic efficacy and minimize adverse effects, moving beyond fixed-activity protocols. Additionally, the exploration of SSTR antagonists represents a novel frontier, potentially improving tumor uptake and retention of radiopharmaceuticals compared to traditional agonists, thereby broadening the therapeutic window and patient eligibility for PRRT.